Interpolymer interactions between the countercharged polymers like Eudragit® EPO (polycation) and hypromellose acetate succinate. PDF | The objective of this investigation was to evaluate the potential of Eudragit EPO nanoparticles (EPO NP) in improving therapeutic efficacy. Download scientific diagram | Molecular structures of (a) MFA, (b) EUDRAGIT® EPO, and (c) EUDRAGIT® L from publication: Stabilization of a.
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The objective of this study was to compare a novel controlled eudrahit tablet formulation based on interpolyelectrolyte complex PEC. The formation of inter-macromolecular ionic bonds between cationic polymer and anionic polymer was investigated using Fourier transform infrared FT-IR spectroscopy and differential scanning calorimetry.
The FT-IR spectra of the tested polymeric matrices are characterized by visible changes in the observed IR region indicating the interaction between chains of two oppositely charged copolymers.
The performance of the in situ formed PEC as a eudrgit for controlled release of drugs was evaluated, using acetaminophen as a model drug.
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The dissolution data of these matrices were fitted to different dissolution models. It was found that drug release followed zero-order kinetics and was controlled by the superposition of the diffusion and erosion. These profiles could be controlled by conveniently modifying the proportion of the polymer ratio, polymer type, and polymer concentration the in the tablets. The use of polyelectrolytes in the design of controlled release drug formulations has received notable attention in the recent years because of the capability of the interpolyelectrolyte complex PEC to achieve more sustained drug release than single polymers 1.
Various types of oppositely charged polyelectrolytes interact electrostatically in aqueous media to form an insoluble solid or PEC 2 — 5. Polymethacrylate polymers have been widely used in pharmaceutical formulations as film-coating agent and as matrix carriers in solid dispersion preparation and in hot-melt extrusion processes 13 — The ratio of dimethylaminoethyl methacrylate groups to butyl methacrylate and methyl methacrylate groups is about 2: The ratio of free carboxyl groups to the ester groups is approximately 1: The carboxylic groups ionize in aqueous media at pH 5.
This enteric polymer is soluble in aqueous media at a pH higher than 5.
HPMCP is cellulose in which some of the hydroxyl groups are replaced with methyl ethers, 2-hydroxypropyl ethers, or phthalyl esters.
Several different types of hypromellose phthalate HP50, HP55, HP55S are commercially available with molecular weights in the range 20,—, The selection of anionic and cationic polymers forming the PEC can be made on the basis of their physicochemical properties such as biocompatibility, physicochemical stability, pH-dependent solubility, and swellability characteristics, etc. The product, PEC complex, was isolated and then dried, before being utilized as a polymeric carrier for modified drug release As an alternative for this lengthy process, we propose in situ EE-enteric polymer polyelectrolyte complexation in an acidic medium simulating the gastric fluid.
Our proposal is dependent on the fact that the acidic groups in the enteric polymers may allow for polymer ionization and interaction with the cationic EE even at low pH values. The aims of this study were as follows:. Acetaminophen was obtained from Mylan laboratories limited Hyderabad, India as a gift sample.
Rudragit monohydrate, hydroxypropyl cellulose, and magnesium stearate were obtained as a gift sample from Mylan laboratories limited Hyderabad, India. Drug and lactose monohydrate were eudrafit through 30 sieve and mixed together for 10 min in a polybag.
Dried granules were mixed with the different proportion of polymers in a polybag for 10 min and further lubricated with magnesium stearate previously passed through 60 mesh sieve. The amount of acetaminophen in matrix tablets was kept constant at mg while the amount of other excipients was varied.
Formulated tablets eudagit subjected to the following physical characterization studies. The hardness of the matrix tablets was examined for five tablets of each batch using a hardness tester Dr.
Tablet thickness of the matrix tablets was examined for six tablets of each batch using an electronic digital caliper. The tablets were weighed initially and rotated at 25 rpm for 4 min, and the samples were then reweighed. The percentage friability edragit calculated using the following equation:. EE and enteric polymer, at 1: Tablets with mg of the polymers were compacted manually from the physical wudragit using a 9-mm punch in a tablet compression machine.
Tablets were exposed to ml of pH 6. For comparative purposes, FT-IR analysis was also performed on pure EE, pure enteric polymers, and an unexposed physical mixture of the polymers.
In vitro drug release testing from tablets was conducted according to the USP 27 apparatus 2 specifications using a dissolution tester Electrolab, India.
The dissolution testing for acetaminophen was conducted in ml of 0. The paddles were rotated at a speed of 50 rpm. The tablets were placed into mL of dissolution medium. Aliquots of 10 mL were withdrawn from the dissolution apparatus at different time intervals and filtered through a cellulose acetate membrane 0. The drug content was determined spectrophotometrically at a wavelength of nm. At each time of withdrawal, 10 mL of fresh medium was replaced into the dissolution flask. The mean of three determinations was used to calculate the drug release from each of the formulation.
The swelling of the polymers upon hydration by the test medium was determined by a method similar to the equilibrium weight gain method as reported earlier The matrix tablets of selected formulations were weighed and placed in tared metallic baskets. These baskets were then immersed in ml of pH 6. At specified time intervals, the baskets containing the matrix tablets were eudragiit, lightly blotted with tissue paper so as to remove excess water and weighed again.
They were then placed back in the dissolution vessel as quickly as possible. The percent degree of swelling was calculated as follows:. The swelling study was done in triplicate for all samples tested.
To study the release kinetics, data obtained from in vitro drug release studies were plotted in various kinetic models: Hence, drug release rate is proportional to the reciprocal of the square root of time. The following plots were made: The model with the highest correlation coefficient was considered to be the best-fitting one. To study the release kinetics from the matrix tablets, the release data were fitted to the well-known exponential equation power law or Korsmeyer-Peppas equationwhich eudragiy often used to describe the drug release behavior from polymeric systems To clarify the release exponent for different batches of matrices, the log value of percentage drug released was plotted against log time for each batch according to eudragt Eq.
In case of Fickian release diffusionaly controlled releasethe n has the limiting values of 0. Case II transport or relaxation controlled delivery; the exponent n is 0.
The non-Fickian release or anomalous transport of drug occurred when the n values are between the limiting values of Fickian and case II transport. The drug release profiles were compared using two model-independent methods, mean dissolution time MDTand similarity factor f 2 MDT was calculated from dissolution data using Eq.
The similarities between two dissolution profiles were assessed by a pair-wise model-independent procedure such as similarity factor f Where n is the number of pull points, R t is the reference profile at time point tand T t is the test profile at the same time point; the value of eudragitt 2 should be between 50 and An f 2 value of suggests that the test and reference profiles are identical and, as the value becomes smaller, the dissimilarity between release profiles increases.
The spectrum of EL Fig. The spectrum of EE Fig. The physical mixture of polymer mixtures showed the bands for the single components data not shown.
As may be appreciated, the latter is different from the rest of the spectra. This might be due to the interaction of protonated dimethylamino group from EE with carboxylate group from anionic polymers.
FT-IR spectrum of pure polymers. FT-IR spectrum of treated polymers. The thickness of the tablets varied depending on bulk density of the dried granules used and the compression force applied. Tablet hardness was found to be good between 12 and 18 kp depending on the compression eduragit applied, and friability was less than 1. The manufactured tablets showed low weight variation indicating that the wet granulation method is an acceptable eop for preparing eudtagit matrix tablets.
Combination of anionic polymers EL and cationic polymers EE for possible sustained release drug delivery has been reported in the literature The drug release from the matrix tablets containing a single polymer as matrix former in 0. Thus, it can be concluded that the use of single anionic or cationic polymer will not provide sustained drug release from the matrix tablets. Hence, matrix tablets containing a combination of anionic and cationic polymers were prepared and the drug release profile was evaluated.
Dissolution eudragi tablets prepared using single polymer in a 0. The drug release profile from these formulations in 0. Formulation with EE and EL F6 showed intermediate drug release profile compared to the other two polymer combinations.
On the other hand, sustained drug release ep observed in pH 6. This slower drug release performance eurragit be attributed to the PEC formation at this pH. Dissolution of eudragiy prepared using different polymer combinations in 0. It is clear that the peo rate is greatly dependent on the concentration of polymers in the formulation.
Evonik EUDRAGIT® E PO Copolymer
Increasing the total amount of polymers in the formulation from mg F10 to mg F9 and mg F8 resulted in a slower release rate and extended drug release from the tablet. The release rate was slowest for the higher polymer concentration formulation F8 with a K value of 7. The release rate was fastest for the lower polymer concentration formulation F10 with a K value of This slow release is because of the formation of a stronger PEC gel structure that delays drug release from the tablet matrix.
The increase in polymer concentration resulted in an increase of the MDT values, where for mg polymer concentration the MDT value was 4.
The slight increase in the MDT value with increasing polymer concentration can be ascribed to the entanglement density of the polymer at higher concentrations. Dissolution of tablets prepared using different polymer concentrations in pH 6.
This is due to the high degree of interaction that could exist as both polymers were ionized and maximum level charge density was obtained especially in acidic and buffer media. It can be observed that the release rate did not vary much for tablets prepared with different polymer grades of HPMC AS.
The calculated MDT values were found to be 4. The release profiles were also analyzed for the similarity factor f 2 values for the assessment of statistical difference or similarity between the sudragit profiles. The f 2 factor value was observed to be It can be seen from Fig. The effect of dissolution media pH 1.